Letrozole and zoledronic acid changed signalling pathways involved in the apoptosis of breast cancer cells

Abstract

Objectives: Oestrogen plays a key role in the development of breast malignancies. Therefore, aromatase inhibitors (e.g. letrozole [LTZ]) are widely used in the treatment of breast cancer. On the other hand, oestrogen is important to the integrity of bone mass. Research has shown that zoledronic acid (ZLA) may prevent osteoporosis. Therefore, the present research aims to investigate the effect of a combination of LTZ and ZLA in the treatment of breast cancer and in reducing osteoporosis in patients with breast cancer. Methods: We used immunocytochemistry and Western immunoblotting techniques in this study. Results: We observed that LTZ inhibited cellular growth of Michigan Cancer Foundation-7 (MCF-7) and T-47D at IC50 (70 0.001) and (140 0.004) nM, respectively, whereas ZLA inhibited cellular growth at IC50 (50 0.005) mM and (150 0.004) mM for MCF-7 and T-47D cell lines, respectively. Interestingly, the LTZ and ZLA combination down-regulated the protein expression of signal transducer and activator of transcription 3 (STAT3) and up-regulated BRCA1 protein expression in both cell lines. Moreover, a notable enhancement in the nuclear localisation of the BRCA1 protein was obtained after treatment of T-47D cells with LTZ for 24 h compared to the control cells. In contrast, there was a reduction in the nuclear localisation of STAT3 protein, which could be an attractive target for inhibition of breast cancer proliferation and progression. Conclusion: Our study has shown that a combination of LTZ and ZLA enhanced apoptosis and inhibited growth of both breast cancer cell lines. This combination can be used to maintain bone integrity in women with breast cancer.